Method for preparing various impurity column [5] arenes by one-pot method and application thereof

Abstract

The invention discloses a method for preparing various mixed column [5] aromatic hydrocarbons by a one-pot method and application of the mixed column [5] aromatic hydrocarbons. The method comprises the following steps: respectively preparing monomers into dimers and trimers by formulating a fragmentation synthesis strategy, finally carrying out cyclization reaction on the dimers and the trimers in different proportions at room temperature, and carrying out column chromatography purification to obtain five different proportions of hetero-pillar arenes. The method is simple and easy to operate, multiple kinds of hetero-pillar arene can be prepared in one pot only through simple inert gas protection, and the total yield is extremely high.

Description

Technical Field

[0001] The present invention relates to the field of organic synthesis, and in particular to a method for preparing various hetero-pillar [5] aromatic hydrocarbons in one pot and its application. Background Art

[0002] Pillar[5]arene is highly biocompatible and has a highly symmetrical columnar structure and a The electron-rich cavity of pyrolysine is an excellent host molecule that can form host-guest complexes with a series of neutral or electron-deficient guest molecules and has been used in many fields.

[0003] In fact, the application of pillar[5]arenes is closely related to the type and nature of the functional groups at both ends of the pillar[5]arenes. Therefore, the preparation of novel functionalized pillar[5]arenes is of great significance for expanding their application in many fields. However, most of the existing pillar[5]arenes can only introduce the same functional groups at both ends to form a D5 symmetrical structure, which greatly limits the multifunctionality, biological activity and application range of functionalized[5]arenes. Therefore, how to prepare novel pillar[5]arenes and introduce different functional groups through simple chemical reactions is of great significance for expanding their application in life sciences and medicine.

[0004] Click chemistry has been widely used in the biomedical field due to its mild chemical reaction conditions, good selectivity and high yield. The construction of clickable hetero[3+2]arenes by simultaneously introducing alkynyl or bromoalkyl groups into hetero[4+1]arenes and thus easily introducing functional groups has been confirmed by previous work. However, the preparation of higher-order clickable hetero[3+2]arenes has not been reported yet due to low yields and difficulties in separation and purification. In summary, there is an urgent need to develop a stable, efficient and simple one-pot method for the efficient synthesis of heteropillar[5]arenes. Summary of the invention

[0005] In view of the defects in the prior art, the present invention proposes a method for preparing various hetero-pillar [5] aromatics in one pot and its application. The present invention uses simple and easily available compounds such as 1,4-bis (2-hydroxyethoxy) benzene, hydroquinone, 2,5-dihydroxyterephthalic acid and 2,5-dihydroxybenzaldehyde as initial raw materials and adopts a fragmentation synthesis strategy to develop a stable and efficient one-pot synthesis method for preparing various hetero-pillar [5] aromatics.

[0006] The present invention provides a hetero-pillar [5] aromatic hydrocarbon prepared based on a one-pot method, wherein the hetero-pillar [5] aromatic hydrocarbon comprises a target compound a, a target compound b, a target compound c, a target compound d, and a target compound e;

[0007] The structural formula of the target compound a is:

[0008]

[0009] The structural formula of the target compound b is:

[0010]

[0011] The structural formula of the target compound c is:

[0012]

[0013] The structural formula of the target compound d is:

[0014]

[0015] The structural formula of the target compound e is:

[0016]

[0017] The present invention also provides a one-pot method for preparing hetero-pillar [5] aromatics, comprising the following steps:

[0018] (1) synthesizing compound E, wherein the compound is a dimer;

[0019] (2) synthesizing compound I, which is a trimer;

[0020] (3) Compound E and Compound I are subjected to a cyclization reaction and purified by column chromatography to obtain hetero-column [5] aromatic hydrocarbons.

[0021] Furthermore, the structural formula of the dimer is:

[0022]

[0023] Furthermore, the structural formula of the trimer is:

[0024]

[0025] Furthermore, the molar ratio of compound E to compound I in step (3) is any one of 1:1, (0.5-1):1, and (1-2):1.

[0026] Preferably, the molar ratio of compound E to compound I in step (3) is 1:1, 1:2, or 2:1.

[0027] Furthermore, the specific process of step (1) is as follows:

[0028] S1: 1,4-bis(2-hydroxyethoxy)benzene, triphenylphosphine and acetonitrile were added to a reaction bottle, and carbon tetrabromide-acetonitrile solution was added to the reaction bottle at low temperature. The solution was stirred at room temperature until it changed from turbid to clear. The reaction was completed, and the solution was filtered, the solvent was dried, and the solution was purified by column chromatography to obtain compound A;

[0029] S2: hydroquinone, potassium carbonate and acetone were added to a reaction bottle, and propyne bromide was added to the reaction bottle under protective gas, and the reaction was allowed to proceed overnight. After the reaction was completed, vacuum filtration was performed, the solvent was dried by spin drying, and column chromatography was performed for purification to obtain compound B;

[0030] S3: 2,5-dihydroxybenzaldehyde, 1,2-dibromoethane and potassium carbonate were added to a reaction bottle, and then dry acetonitrile was added, and the reaction was carried out in an oil bath under protective gas. After the reaction was completed, vacuum filtration was performed, the solvent was dried by spin drying, and column chromatography was performed for purification to obtain compound C;

[0031] S4: dissolving the compound C described in step S3 in tetrahydrofuran and methanol, adding sodium borohydride in an ice bath, stirring at room temperature, and after the reaction is complete, adding ammonium chloride solution to quench, extracting with dichloromethane, drying with anhydrous sodium sulfate, and then spinning off the solvent, and purifying with column chromatography to obtain compound D;

[0032] S5: Take the compound D described in step S4 and the compound A, dissolve them in dichloromethane, add trifluoroacetic acid, stir at room temperature overnight, and after the reaction is completed, add saturated sodium bicarbonate solution to quench, extract with dichloromethane, dry with anhydrous sodium sulfate, and then spin-dry the solvent, wet load, and purify by column chromatography to obtain compound E.

[0033] Furthermore, the specific process of step (2) is as follows:

[0034] i): 2,5-dihydroxyterephthalic acid and methanol were placed in a reaction flask, thionyl chloride was added under a protective gas ice bath, and the reaction was carried out at 60° C. overnight. After the reaction was completed, the solvent was dried by spin drying, and column chromatography was performed using pure dichloromethane to obtain compound F;

[0035] ii): Compound F described in step i), potassium carbonate, iodomethane and dimethylformamide are placed in a reaction flask, stirred at 60° C. under protective gas, and then propargyl bromide is added dropwise. After the reaction is completed, the mixture is cooled to room temperature, filtered, dried over anhydrous sodium sulfate, the solvent is dried, and purified by column chromatography to obtain compound G;

[0036] iii): Compound G described in step ii) and tetrahydrofuran are placed in a reaction bottle, lithium hydride is added under ice bath, and the mixture is stirred at room temperature. After the reaction is completed, sodium sulfate decahydrate is added to quench the mixture, and the mixture is filtered with suction, and washed with tetrahydrofuran, dichloromethane, ethyl acetate and methanol. The solvent is then dried to obtain compound H;

[0037] iiii): Compound H described in step iii), compound B and dichloromethane are placed in a reaction flask, trifluoroacetic acid is added to react at room temperature, and after the reaction is completed, a saturated sodium bicarbonate solution is added to quench, extracted with dichloromethane, dried over anhydrous sodium sulfate, the solvent is spin-dried, and purified by column chromatography to obtain compound I.

[0038] Furthermore, the specific process of step (3) is as follows: placing the compound E and compound I in a reaction bottle, adding dry 1,2-dichloroethane and paraformaldehyde, adding boron trifluoride ether under argon, reacting at room temperature, and after the reaction is completed, quenching with saturated sodium bicarbonate solution, extracting with dichloromethane, drying with anhydrous sodium sulfate, spin drying, and purifying by column chromatography to obtain hetero-column [5] aromatic hydrocarbons.

[0039] The present invention also provides the use of the hetero-pillar [5] aromatic hydrocarbon in the preparation of gas adsorption materials.

[0040] The present invention also provides the use of the heteropillar [5] aromatic hydrocarbon in the preparation of an antibacterial and / or antiviral drug sustained-release agent or solubilizer or dispersant or drug delivery.

[0041] In summary, compared with the prior art, the present invention achieves the following technical effects: the present invention prepares monomers into dimers and trimers respectively through a fragment synthesis strategy, and finally, after the dimers and trimers of different proportions are subjected to a cyclization reaction at room temperature, five different proportions of hetero-columnar aromatics can be obtained by column chromatography purification. This method does not require harsh conditions, and only requires simple inert gas protection to prepare a variety of hetero-columnar aromatics in one pot, and the total yield is extremely high, which solves the defects of the prior art that the synthesis and separation of hetero-columnar aromatics are difficult and single. In addition, the preparation method of the target compound of the present invention has mild reaction conditions, simple synthesis, and is suitable for industrial large-scale production. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for use in the embodiments are briefly introduced below. It should be understood that the following drawings only show certain embodiments of the present invention and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other related drawings can be obtained based on these drawings without creative work.

[0043] Figure 1 is a structural diagram of the hetero-pillar [5] aromatic hydrocarbon prepared by the one-pot method of the present invention; wherein a is the structural diagram of the target compound a; b is the structural diagram of the target compound b; c is the structural diagram of the target compound c; d is the structural diagram of the target compound d; and e is the structural diagram of the target compound e;

[0044] Figure 2 The target compound a of the present invention is 1 H-NMR spectrum;

[0045] Figure 3 The target compound b of the present invention is 1 H-NMR spectrum;

[0046] Figure 4 The target compound c of the present invention is 1 H-NMR spectrum;

[0047] Figure 5 The target compound d of the present invention is 1 H-NMR spectrum;

[0048] Figure 6 The target compound e of the present invention is 1 H-NMR spectrum;

[0049] Figure 7 The compound 4 of the present invention 1 H-NMR spectrum;

[0050] Figure 8 is the carbon spectrum of compound 4 of the present invention;

[0051] Fig. 9 This is the E.Coli MIC graph of compound 4 of the present invention; wherein E.Coli represents Escherichia coli;

[0052] Fig.10 It is the MIC graph of the compound 4 of the present invention for the PA01 bacteria; wherein PA01 represents Pseudomonas aeruginosa;

[0053] Fig.11 It is the SA bacteria MIC graph of compound 4 of the present invention; wherein SA represents Staphylococcus aureus. DETAILED DESCRIPTION

[0054] In order to enable those skilled in the art to better understand the scheme of the present invention, the technical scheme in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only embodiments of a part of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work should fall within the scope of protection of the present invention.

[0055] The one-pot method for preparing various hetero-pillar [5] aromatics of the present invention comprises preparing monomers into dimers and trimers respectively through a fragmentation synthesis strategy, and finally performing a cyclization reaction of dimers and trimers in different proportions in a greenhouse, followed by column chromatography purification to obtain hetero-pillar [5] aromatics in different proportions. The structures of the hetero-pillar [5] aromatics are respectively as follows: Figure 1As shown, the hetero-pillar [5] aromatic hydrocarbons include target compound a, target compound b, target compound c, target compound d, and target compound e.

[0056] Example 1

[0057] This embodiment provides a one-pot method for preparing a variety of hetero-pillar [5] aromatics. A dimer is synthesized by a fragment synthesis strategy, and the dimer is bis (2,5-bis (2-bromoethoxy) phenyl) methane, referred to as compound E. The method comprises the following steps:

[0058] (1) Synthesis of Compound A:

[0059]

[0060] Take 1,4-bis(2-hydroxyethoxy)benzene (4 g, 20 mmol), triphenylphosphine (11.5 g, 44 mmol) and 60 mL of acetonitrile in a round-bottom flask, take carbon tetrabromide (14.5 g, 44 mmol) and 20 mL of acetonitrile in a constant pressure dropping funnel, slowly add carbon tetrabromide-acetonitrile solution into the round-bottom flask at -20°C, stir at room temperature for 4 h after the addition is completed, the solution changes from turbid to clear, the reaction is completed, filter, spin-dry the solvent, and pass through a column with a developing solvent PE:DCM = 1:1 to obtain a white solid A: 5.03 g, with a yield of 81.84%.

[0061] (2) Synthesis of Compound B:

[0062]

[0063] Take hydroquinone (2g, 18.175mmol), potassium carbonate (12.5g, 90.875mmol) and acetone 20mL in a round-bottom flask, add propargyl bromide (4mL, 45.5mmol) at 60℃ under nitrogen protection and react overnight. After the reaction is completed, vacuum filter, spin-dry the solvent, and pass it through a column with a developing solvent PE:EA=20:1 to obtain a light yellow oil. After standing for a while, a light yellow solid B: 3.29g is obtained, and the yield is 97.28%.

[0064] (3) Synthesis of Compound C:

[0065]

[0066] Take 2,5-dihydroxybenzaldehyde (15 g, 108.67 mmol), 1,2-dibromoethane (74 mL, 858.72 mmol) and potassium carbonate (35 g, 108 mmol) in a round-bottom flask, add 250 mL of dry acetonitrile, react in a 60 ° C oil bath under nitrogen protection for 5 days. After the reaction is completed, vacuum filter, spin dry the solvent, and pass through a column with a developing solvent DCM: PE = 1: 1 to obtain a light yellow solid C: 9.23 g, with a yield of 25.39%.

[0067] (4) Synthesis of Compound D:

[0068]

[0069] Take the light yellow solid C (3.327 g, 9.53 mmol) and dissolve it in tetrahydrofuran (20 mL) and methanol (20 mL). Add sodium borohydride (360 mg, 9.53 mmol) in small amounts several times under an ice bath. After the addition, stir at room temperature for 1 h. After the reaction is completed, add ammonium chloride solution to quench, extract with dichloromethane, dry with anhydrous sodium sulfate, and spin dry the solvent. Use the developing solvent DCM:PE=1:2 to wash away the impurities, and then change to pure dichloromethane to obtain the product, and obtain white product D: 3.321 g, with a yield of 99%.

[0070] (5) Synthesis of Compound E:

[0071]

[0072] Take white solid D (5.8g, 16.5mmol) and compound A (24g, 74.1mmol) and dissolve them in 200mL of dichloromethane, add trifluoroacetic acid (50mL, 285.6mmol) and stir at room temperature overnight. After the reaction is completed, add saturated sodium bicarbonate solution to quench, extract with dichloromethane, dry with anhydrous sodium sulfate and spin dry the solvent, wet sample, and pass through the column with developing agent DCM:PE=1:3 to obtain white product E: 4.38g, with a yield of 40.47%. The white product E is a dimer, and the dimer is (di, 5-di(2-bromoethoxy)phenyl)methane.

[0073] Example 2

[0074] This embodiment provides a one-pot method for preparing a variety of heteropillar [5] aromatics. A trimer is synthesized by a fragment synthesis strategy, and the trimer is 2,2'-((2,5-bis(prop-2-yn-1-yloxy)-1,4-phenylene)bis(methylene))bis(1,4-bis(prop-2-yn-1-yloxy)benzene), referred to as compound I. The method comprises the following steps:

[0075] The synthetic route of compound I is as follows:

[0076]

[0077] (1) Synthesis of Compound F:

[0078] Take 2,5-dihydroxyterephthalic acid (11 g, 55.51 mmol) and 210 mL of methanol in a three-necked flask, add dichlorothionyl (49.5 mL, 697.34 mmol) dropwise in an ice bath under nitrogen protection, and react at 60 ° C overnight after the reaction. After the reaction, the solvent is dried and pure dichloromethane is used to pass through a column to obtain a yellow-green solid F: 12.437 g, with a yield of 99.12%.

[0079] (2) Synthesis of Compound G:

[0080] Take yellow-green solid F (6 g, 26.54 mmol), potassium carbonate (15 g, 108.53 mmol), iodomethane (880 mg, 7.59 mmol) and 100 mL of dimethylformamide in a three-necked flask, stir at 60 ° C for 30 minutes under nitrogen protection, then add propargyl bromide (9.2 mL, 106.72 mmol) dropwise with a constant pressure dropping funnel, and continue the reaction for 2 days. After the reaction is completed, cool to room temperature, filter, dry over anhydrous sodium sulfate, spin dry the solvent, and pass through a column with a developing solvent PE: EA = 5: 1 to obtain a light yellow solid G: 4.6 g, with a yield of 57.38%.

[0081] (3) Synthesis of Compound H:

[0082] Take light yellow solid G (11g*2, 36.42mmol) and 150mL*2 tetrahydrofuran in a round-bottom flask, add lithium hydride (2.76g*2, 72.84mmol) in small amounts several times under ice bath, and then stir at room temperature for 5h. After the reaction is completed, add sodium sulfate decahydrate to quench. Filter by suction, wash the filter cake with tetrahydrofuran, dichloromethane, ethyl acetate and methanol, spin dry the solvent, and obtain light yellow product H: 11.4g, with a yield of 63.6%.

[0083] (4) Synthesis of Compound I:

[0084] H (3 g, 12.19 mmol), B (16 g, 85.99 mmol) and 150 mL of dichloromethane were placed in a round-bottom flask, trifluoroacetic acid (32 mL, 429.95 mmol) was added and reacted at room temperature for 5 h. After the reaction was completed, a saturated sodium bicarbonate solution was added to quench, and the mixture was extracted with dichloromethane, dried over anhydrous sodium sulfate, and the solvent was dried by spin drying. PE:DCM=1:3 was passed through a column to obtain a white solid I: 1.71 g, with a yield of 24.1%. The white solid I is a trimer, and the trimer is 2,2'-((2,5-bis(prop-2-yn-1-yloxy)-1,4-phenylene)bis(methylene))bis(1,4-bis(prop-2-yn-1-yloxy)benzene).

[0085] Example 3

[0086] This embodiment provides a one-pot method for preparing a variety of hetero-pillar [5] aromatics. Five hetero-pillar aromatics in different proportions can be obtained by subjecting the above-mentioned compound E and compound I to a cyclization reaction at room temperature and then purifying by column chromatography. The specific steps are as follows:

[0087] Compound E and compound I were taken in a three-necked flask according to the ratio in Table 1, 50 mL of dry 1,2-dichloroethane and paraformaldehyde (281 mg, 9.27 mmol) were added, argon was replaced, and boron trifluoride etherate (763 μL, 6.18 mmol) was added under argon to react at room temperature for 30 min. After the reaction was completed, saturated sodium bicarbonate solution was quenched, dichloromethane was extracted, dried over anhydrous sodium sulfate, spin-dried, and PE:DCM=5:4 was passed through a column to obtain the products listed in Table 1.

[0088] Table 1 Mixing ratio of compound E and compound I and product yield results

[0089]

[0090]

[0091] The various heteroaromatic hydrocarbons prepared in Table 1 are product a, product b, product c, product d, and product e, respectively. 1 H-NMR spectrum Figure 2 As shown; product b 1 H-NMR spectrum Figure 3 As shown; product c 1 H-NMR spectrum Figure 4 As shown; product d 1 H-NMR spectrum Figure 5 As shown; product e 1 H-NMR spectrum Figure 6 As shown. The above-mentioned product a, product b, product c, product d, and product e are the target compound a, target compound b, target compound c, target compound d, and target compound e of the present invention, respectively. When the molar ratio of compound E to compound I is 1:1, the total yield of hetero-column [5] aromatics is 64.45%; when the molar ratio of compound E to compound I is 1:2, the total yield of hetero-column [5] aromatics is 91.56%; when the molar ratio of compound E to compound I is 1:2, the total yield of hetero-column [5] aromatics is 96.01%; the above results show that the total yield of hetero-column [5] aromatics prepared by the one-pot method of the present invention is extremely high, and the method is simple and easy to operate.

[0092] Example 4

[0093] The one-pot method for preparing hetero-pillar aromatics comprises the following specific steps:

[0094]

[0095] (1) Compound d (100 mg, 0.07752 mmol) and compound Ac (375 mg, 0.9302 mmol), 2 mL of dichloromethane and 2 mL of water were placed in a 10 mL EP tube. After replacing the argon atmosphere, copper sulfate (4 mg, 0.0155 mmol) and sodium ascorbate (10 mg, 0.05115 mmol) were added. The argon atmosphere was replaced again and the reaction was carried out at room temperature for 2 days. After the plate reaction was completed, ammonium chloride solution was added for washing, dichloromethane was used for extraction, and the solvent was dried over anhydrous sodium sulfate and then dried by rotary evaporation. The impurities were washed with pure dichloromethane and then replaced with a developing solvent of DCM:MeOH = 40:1 for column chromatography to obtain 234 mg of yellow solid compound 1 with a yield of 82.3%.

[0096] (2) Compound 1 (234 mg, 0.0638 mmol) and sodium azide (42 mg, 0.638 mmol) were placed in a sealed tube, 4 mL of DMF was added, and the mixture was reacted in an oil bath at 75°C under nitrogen protection for 1 d. After the reaction was completed, water and saturated brine were added for washing, and the mixture was extracted with ethyl acetate and then with dichloromethane. The mixture was spin-dried to obtain 190 mg of white solid compound 2 with a yield of 77.5%.

[0097] (3) Compound 2 (190 mg, 0.0495 mmol), compound Bc (197 mg, 0.396 mmol), 2 mL of dichloromethane and 2 mL of water were placed in a 10 mL EP tube. After replacing the argon atmosphere, copper sulfate (2.5 mg, 0.01 mmol) and sodium ascorbate (6.5 mg, 0.0328 mmol) were added. The argon atmosphere was replaced again and the reaction was carried out at room temperature for 2 d. After the plate reaction was completed, the mixture was washed with ammonium chloride solution, extracted with dichloromethane, dried over anhydrous sodium sulfate and the solvent was dried by spin drying. The impurities were washed with pure dichloromethane and then replaced with a developing solvent of DCM:MeOH = 30:1 and passed through a column to obtain 254 mg of yellow solid compound 3 with a yield of 92.2%.

[0098] (4) Compound 3 (200 mg, 0.03432 mmol) and 5 mL of methanol were placed in a round-bottom flask, and sodium methoxide (56 mg) was added under ice bath. After the addition, the mixture was reacted at room temperature for 16 h. After the reaction was completed, cationic resin was added to neutralize the pH to 7, and then the mixture was filtered and dried to obtain an oily substance. The obtained oily substance was placed in a round-bottom flask with 3 mL of trifluoroacetic acid and 3 mL of dichloromethane, and reacted at room temperature for 1 day. After the reaction was completed, the mixture was dried and washed with ether three times to obtain a brown solid compound 4 with a total of 120 mg and a yield of 70.8%. Compound 4 1 H-NMR spectrum Figure 7 As shown; the carbon spectrum is as Figure 8 shown.

[0099] The minimum inhibitory concentration (MIC) activity experiment was performed on compound 4, and the specific steps were as follows:

[0100] (1) Take 5 mL of LSB medium and place it in a centrifuge tube, add one loop of bacterial solution (taken from -80°C), and culture it in a constant temperature shaking incubator at 37°C for 18-24 h;

[0101] (2) Adjust the bacterial solution concentration to 5×10 5 CFU / mL(OD 600 =0.1, the bacterial concentration is 1×10 8 CFU / mL);

[0102] (3) Take a 96-well plate and number it. Add 150 μL LSB broth to the first column (A1-H1) as a sterile blank control. Add 150 μL bacterial solution to the second column (A2-H2) as a solvent control. Take 10 μL of the mother solution of compound 4 and add it to the third column (A3-H3). Add 5×10 5 CFU / mL bacterial solution 290μL, add 150μL of bacterial solution to wells in columns 4-12, mix in column 3, take 150μL from wells in column 3 and add to wells in column 4, dilute equally to wells in column 12 in this way, take 150μL from wells in column 12 and discard; (Compound 4 was diluted 30 times in total, the final concentration of the drug was 320μmol / L, 160μmol / L, 80μmol / L, 40μmol / L, 20μmol / L, 10μmol / L, 5μmol / L, 2.5μmol / L, 1.25μmol / L, 0.625μmol / L), the final concentration of bacterial solution was 5×10 5 CFU / mL, total volume 150μL). The 96-well plate was placed in a 37°C constant temperature incubator for 18-24h. The activity test results are as follows Fig. 9 , Fig.10 and Fig.11As shown, the experimental results show that compound 4 has an antibacterial effect on E. coli, PA01 and SA bacteria, wherein the antibacterial concentration range for E. coli is ≥ 0.625 μmol / L, the antibacterial concentration for PA01 is ≥ 10 μmol / L, and the antibacterial concentration range for SA is ≥ 40 μmol / L. Therefore, compound 4 has the best antibacterial effect on E. coli. The hetero-pillar [5] aromatic hydrocarbons of the present invention have high biocompatibility and specific structural characteristics, which makes them have a wide range of application potentials in the fields of gas adsorbents, sustained-release agents for antibacterial and antiviral drugs, solubilizers, dispersants, drug delivery and cosmetics. It is particularly worth mentioning that by adjusting the molar ratio of dimers and trimers, the ratio of the final product can be accurately controlled, thereby providing more flexibility and selectivity for research and application in related fields.

[0103] In summary, the present invention prepares monomers into dimers and trimers respectively through a fragment synthesis strategy, and finally, after the dimers and trimers of different proportions are subjected to a cyclization reaction at room temperature, five different proportions of hetero-columnar aromatics can be obtained by column chromatography purification. This method does not require harsh conditions, and only requires simple inert gas protection to prepare a variety of hetero-columnar aromatics in one pot, and the total yield is extremely high, which can solve the defects of the prior art that the synthesis and separation of hetero-columnar aromatics are difficult and single. In addition, the preparation method of the target compound of the present invention has mild reaction conditions, simple synthesis, and is suitable for industrial large-scale production.

[0104] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A one-pot method for preparing hetero-pillar[5]arene. It is characterized in that The hetero-pillar [5] aromatic hydrocarbons include target compound a, target compound b, target compound c, target compound d, and target compound e; The structural formula of the target compound a is: The structural formula of the target compound b is: The structural formula of the target compound c is: The structural formula of the target compound d is: The structural formula of the target compound e is:

2. A one-pot method for preparing hetero-pillar[5]arene, It is characterized in that The following steps are involved: (1) synthesizing compound E, wherein the compound is a dimer; (2) synthesizing compound I, which is a trimer; (3) The compound E and the compound I are subjected to a cyclization reaction and purified by column chromatography to obtain hetero-column [5] aromatic hydrocarbons.

3. The method according to claim 2, It is characterized in that The structural formula of the dimer is:

4. The method according to claim 2, It is characterized in that The structural formula of the trimer is:

5. The method according to claim 2, It is characterized in that The molar ratio of compound E to compound I in step (3) is any one of 1:1, (0.5-1):1, and (1-2):

1.

6. The method according to claim 2, It is characterized in that The specific process of step (1) is as follows: S1: 1,4-bis(2-hydroxyethoxy)benzene, triphenylphosphine and acetonitrile were added to a reaction bottle, and carbon tetrabromide-acetonitrile solution was added to the reaction bottle at low temperature. The solution was stirred at room temperature until it changed from turbid to clear. The reaction was completed, and the solution was filtered, the solvent was dried, and the solution was purified by column chromatography to obtain compound A; S2: hydroquinone, potassium carbonate and acetone were added to a reaction bottle, and propyne bromide was added to the reaction bottle under protective gas, and the reaction was allowed to proceed overnight. After the reaction was completed, vacuum filtration was performed, the solvent was dried by spin drying, and column chromatography was performed for purification to obtain compound B; S3: 2,5-dihydroxybenzaldehyde, 1,2-dibromoethane and potassium carbonate were added to a reaction bottle, and then dry acetonitrile was added to react in an oil bath under protective gas. After the reaction was completed, vacuum filtration was performed, the solvent was dried by spin drying, and column chromatography was performed for purification to obtain compound C; S4: dissolving the compound C described in step S3 in tetrahydrofuran and methanol, adding sodium borohydride in an ice bath, stirring at room temperature, and after the reaction is complete, adding ammonium chloride solution to quench, extracting with dichloromethane, drying with anhydrous sodium sulfate, and then spinning off the solvent, and purifying with column chromatography to obtain compound D; S5: Take the compound D described in step S4 and the compound A described in claim 6, dissolve them in dichloromethane, add trifluoroacetic acid, stir at room temperature overnight, and after the reaction is completed, add saturated sodium bicarbonate solution to quench, extract with dichloromethane, dry with anhydrous sodium sulfate, and then spin-dry the solvent, wet load, and purify by column chromatography to obtain compound E.

7. The method according to claim 2, It is characterized in that The specific process of step (2) is as follows: i): 2,5-dihydroxyterephthalic acid and methanol were placed in a reaction flask, thionyl chloride was added under a protective gas ice bath, and the reaction was carried out at 60° C. overnight. After the reaction was completed, the solvent was dried by spin drying, and column chromatography was performed using pure dichloromethane to obtain compound F; ii): Compound F described in step i), potassium carbonate, iodomethane and dimethylformamide are placed in a reaction flask, stirred at 60° C. under protective gas, and then propargyl bromide is added dropwise. After the reaction is completed, the mixture is cooled to room temperature, filtered, dried over anhydrous sodium sulfate, the solvent is dried, and purified by column chromatography to obtain compound G; iii): Compound G described in step ii) and tetrahydrofuran are placed in a reaction bottle, lithium hydride is added under ice bath, and the mixture is stirred at room temperature. After the reaction is completed, sodium sulfate decahydrate is added to quench the mixture, and the mixture is filtered with suction, and washed with tetrahydrofuran, dichloromethane, ethyl acetate and methanol. The solvent is then dried to obtain compound H; iiii): Compound H described in step iii), compound B described in claim 6 and dichloromethane are placed in a reaction bottle, trifluoroacetic acid is added to react at room temperature, and after the reaction is completed, a saturated sodium bicarbonate solution is added to quench, extracted with dichloromethane, dried over anhydrous sodium sulfate, the solvent is spin-dried, and purified by column chromatography to obtain compound I.

8. The method according to claim 2, It is characterized in that The specific process of step (3) is as follows: placing the compound E and compound I in a reaction bottle, adding dry 1,2-dichloroethane and paraformaldehyde, adding boron trifluoride ether under argon, reacting at room temperature, and after the reaction is completed, quenching with saturated sodium bicarbonate solution, extracting with dichloromethane, drying with anhydrous sodium sulfate, spin drying, and purifying by column chromatography to obtain hetero-column [5] aromatic hydrocarbons.

9. Use of the hetero-pillar [5] aromatic hydrocarbons as claimed in claim 1 in the preparation of gas adsorption materials.

10. Use of the impurity column [5] according to claim 1 in the preparation of antibacterial and / or antiviral drug sustained-release agents or solubilizers, dispersants, drug delivery and cosmetics.

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